Nature Genetics
27, 399 - 405 (2001)
doi:10.1038/86898
Learning deficits, but normal development and tumor predisposition, in mice lacking exon 23a of Nf1Rui M. Costa1, 6, Tao Yang2, 5, 6, Duong P. Huynh3, Stefan M. Pulst3, David H. Viskochil4, Alcino J. Silva1
& Camilynn I. Brannan21
Departments of Neurobiology, Psychiatry and Psychology, BRI, UCLA, Los Angeles, California, USA. 2
Department of Molecular Genetics and Microbiology, Center for Mammalian Genetics, and the University of Florida Brain Institute, University of Florida College of Medicine, Gainesville, Florida, USA. 3
Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA. 4
Division of Medical Genetics, University of Utah, Salt Lake City, Utah, USA. 5
Present address: Brigham and Woman's Hospital, Boston, Massachusetts, USA. 6
These authors contributed equally to this work.
Correspondence should be addressed to Alcino J. Silva Silvaa@mednet.ucla.edu or Camilynn I. Brannan Brannan@mgm.ufl.eduNeurofibromatosis type 1 (NF1) is a commonly inherited autosomal dominant disorder. Previous studies indicated that mice homozygous for a null mutation in Nf1 exhibit mid-gestation lethality, whereas heterozygous mice have an increased predisposition to tumors and learning impairments. Here we show that mice lacking the alternatively spliced exon 23a, which modifies the GTPase-activating protein (GAP) domain of Nf1, are viable and physically normal, and do not have an increased tumor predisposition, but show specific learning impairments. Our findings have implications for the development of a treatment for the learning disabilities associated with NF1 and indicate that the GAP domain of NF1 modulates learning and memory.
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